The objective of this proposal is to evaluate the possible role of estrogens, progesterone, oxytocin, prostaglandins and catecholamines in the initiation of parturition in women. On the basis of considerable evidence, it appears that a combination of these hormones may act either directly on the myometrium to affect myometrial contraction, or they may act in decidua to increase the production of prostaglandins, which ultimately trigger myometria contractions. Our main thesis is that initiation of labor in women is triggered not by changes in circulating hormone levels, but by changes in target tissue sensitivity to existing hormone levels mediated by changes in the affinity or the number of their receptors. Furthermore, it appears that there is a complex interdependence in the actions of the various hormones, each affecting the synthesis, metabolism, or the response of the others. We therefore propose to characterize hormone receptors in the myometrium and decidua, to study the factors regulating receptor number and affinity, and to measure changes in receptor concentrations and affinity during pregnancy and labor. Specifically, we propose to (a) characterize estrogen, progesterone, oxytocin, prostaglandin E1 an F2alpha, alpha-adrenergic and beta-adrenergic receptors in the myometrium and to measure their levels during pregnancy and labor; (b) study the regulation of these receptors by examining changes in their levels during the menstrual cycle and investigate the mechanisms regulating the translocation of cytoplasmic steroid hormone receptors to the nucleus; (c) measure the levels of estrogen, progesterone, and oxytocin receptors during pregnancy and labor in decidua, since these hormones may be involved in the regulation of decidual prostaglandin synthesis; (d) develop a system of myometrial smooth muscle cells in monolayer culture to be used as a model to study hormone receptor regulation and the hormonal control of myometrial cell growth and contractility; (e) determine whether pregnancy abnormalities such as prolonged pregnancy, premature labor, and premature rupture of the membranes are associated with abnormal changes in the levels of any of these receptors in the decidua and/or myometrium; and (f) compare the levels of oxytocin receptors in myometrium and decidua of patients with premature rupture of the membranes who either do not respond to oxytocin or whose labor is induced by oxytocin.